Constituents: Borage's main constituent of interest is gamma-linolenic acid (GLA), which is responsible for most of the pharmacological effects below.5 Borage oil also contains the microsomal desaturase, Delta6-fatty acid desaturase, which shows homology to the small hemoprotein cytochrome (Cyt) b5.15

Antibacterial activity: In an in vitro study of 25 botanical aqueous extracts, borage was one of the most efficient antibacterial extracts against Helicobacter pylori.4

Anti-inflammatory effects: Based on recent research, Kast et al. hypothesized that borage oil's anti-inflammatory effects may be due to the gamma-linolenic acid component of borage oil, which suppresses tumor necrosis factor-alpha synthesis by increasing prostaglandin E and cAMP levels.9 The authors continued that if this biochemical path is correct, then "concomitant non-steroidal anti-inflammatory drug use would tend to undermine borage oil effects, and borage oil would be contraindicated in pregnancy given the teratogenic and labor inducing effects of prostaglandin E agonists."

Antiplatelet effects: According to a review article and a study on GLA (source unspecified), borage seed oil may potentially increase the risk of bleeding or potentiate the effects of warfarin therapy.6,12 However, in a study of healthy volunteers, the therapeutic dosage of 3g daily of borage oil supplementation did not affect platelet aggregation.13

Cardiovascular effects: In a randomized, double-blind study, normotensive subjects ingested 4.5mL daily for four weeks to assess the effects of dietary safflower (control, N=10), borage (N=9), and fish oil (N=10) on cardiovascular responses to lower-body negative pressure.14 Borage oil significantly altered plasma norepinephrine and vasoconstrictor responses to -40 mmHg lower-body negative pressure, as well as the reflex vasodilation on its cessation. The authors hypothesize that borage oil may augment arterial baroreflex control of vascular resistance.

Dermatologic activity: In a study of the influence of nine lipids on normal skin and skin irritated by sodium lauryl sulfate, a single application of borage oil had no effect on irritation.16

Fatty acid activity: Various studies have been conducted to elucidate the effect that borage oil or its primary constituent, gamma-linolenic acid (GLA), has on serum and cellular fatty acids. According to studies in humans, ingestion of GLA increases its metabolite dihomo-gamma-linolenic acid (DGLA).5,11,1,17,18 The increase of DGLA in turn increases the level of its metabolite 15-hydroxyeicosatrienoic acid (15-HETrE) and other chemicals, which are known anti-inflammatories and antiproliferatives.5,1 GLA also slightly increases arachidonic acid (AA) levels.17,19,11 However, some researchers hypothesize that GLA should increase arachidonic acid levels much higher, and thus, arachidonic acid may be inhibited by eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Nonetheless, this interaction does not seem to be occurring, and GLA has a limited impact on arachidonic acid levels.19,11,18 Interestingly, GLA consumed with alpha-linolenic acid (ALA) significantly, yet negligibly, increased omega 3 and eicosapentaenoic acid in vegans' serum cholesterol.10 In another human study, a combination of GLA and stearidonic acid also increased the proportion of eicosapentaenoic acid in some lipid fractions.17

Hematological effects: In an in vitro study in platelets of men who had consumed borage oil, borage oil altered the fatty acid composition of the platelet phospholipids, including a reversible rise in the DGLA and a decrease in n-3 polyunsaturated fatty acids.18

Immunological effects: In an in vitro study, GLA from borage oil dose-dependently reduced tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-10 levels to 60% of control levels.2 These effects were not altered by the addition of indomethacin, indicating that DGLA affects TNF-alpha and IL-10 levels independently of COX activation. In addition, ingestion of GLA seems to reduce polymorphonuclear generation of proinflammatory leukotriene B4, although this effect does not appear to be dose-dependent.7 In rheumatoid arthritis subjects, GLA suppressed T lymphocyte proliferation, which is related to the propagation of joint tissue injury.8 This finding is supported by a more in-depth animal study, in which mice fed borage oil had increased T-helper 1-like responses and decreased T-helper 2-like responses, and possibly enhanced suppressor cell or T-helper 3-like activity.3

Pharmacodynamics/Kinetics:

Absorption: In a study using full thickness human skin, Karia et al. simulated the absorption of tamoxifen and borage oil into breast tissue.20 The tissue was dosed with 500mcL saturated solution of tamoxifen in borage oil (25% GLA). The cumulative permeation at 24 hours was 764.3 ± 94.2mcg/cm2 for GLA and 5.44 ± 0.67mcg/cm2 for tamoxifen; the tamoxifen permeation is comparable to the amount of tamoxifen associated with cancerous breast tissue from a 20mg oral dose. The ratio of GLA/tamoxifen permeated at different time points was quite consistent, which the authors hypothesize may be due to the association of 2.5 molecules of GLA with each molecule of tamoxifen in the permeation process.

Metabolism: In an in vitro study in human neutrophils, GLA from borage oil rapidly elongated (by the addition of two carbons) to dihomo-gamma-linolenic acid (DGLA), which is incorporated into neutral lipids, specifically triacylglycerides.21 To determine whether DGLA could be mobilized from cellular glycerolipids, neutrophils were stimulated with ionophore A23187 and fatty acid levels were determined. DGLA and arachidonic acid (AA) were both released during stimulation, and the quantities of DGLA mobilized increased threefold after in vitro GLA supplementation.